Maintenance Rituximab Post-ASCT Associated With Improved OS in MCL

Jason Harris

Published: Tuesday, Sep 19, 2017

Matthew G. Mei, MD

Patients who received maintenance therapy with rituximab (Rituxan) following autologous stem cell transplantation (ASCT) as treatment for mantle cell lymphoma (MCL) had a survival advantage, according to results from a retrospective single-center study.

Among 191 patients with MCL treated at City of Hope National Medical Center in Duarte, California, 92% received rituximab before ASCT and 39% received rituximab following ASCT. Researchers found that maintenance rituximab posttransplantation was the strongest prognostic indicator for both overall survival (OS) and progression-free survival (PFS). Maintenance rituximab conferred a relative risk (RR) for OS of 0.17 (95% CI, 0.07-0.38) and of 0.25 (95% CI, 0.14-0.44) for PFS.

“Our data identify maintenance rituximab after ASCT as the strongest factor resulting in significant improvement of PFS and OS in all patients,” first author Matthew G. Mei, MD, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, and coinvestigators wrote.

“In patients who were already in a PET-negative [first complete remission] before ASCT, maintenance rituximab remained strongly associated with superior PFS and OS, especially when initiated in the first 180 days post-ASCT. In fact, patients who received maintenance rituximab had a 75% risk reduction in progression and 83% in death,” added Mei et al.

Researchers evaluated data on patients treated from January 1997 to November 2013 for this study. Median age at diagnosis was 59 years and 74% were men. Nearly all patients (98%) had stage III or IV disease, and 52% had intermediate- or high-risk disease.

Two-thirds of patients had received 1 frontline therapy prior to ASCT. More than half (56%) received a frontline regimen containing high-dose cytarabine, either hyper-CVAD (n = 93), the Nordic regimen (n = 10), or both (n = 3).

One hundred forty-four patients (75%) underwent ASCT in first complete remission. Twenty-eight patients (15%) were transplanted in first partial remission, and 19 (10%) in a second remission or later.

For all patients, 5-year OS was 71% (95% CI, 63-77) and PFS was 53% (95% CI, 45-60). Sixty-six patients (88%) who received maintenance rituximab were in first complete remission compared with 67% for those who did not receive maintenance rituximab (P = .001).

For the subset of patients who had PET data available and were in a PET-negative first complete remission at ASCT (n = 105), maintenance rituximab was significantly associated with superior OS (RR, 0.17; 95% CI, 0.05-0.59) and PFS (RR, 0.20; 95% CI, 0.09-0.43).

For all patients who started maintenance rituximab within 180 days post-ASCT, the 5-year OS was 88% (95% CI, 75-95) versus 63% (95% CI, 53-71) for patients who did not receive maintenance rituximab by that point (P <.001). Five-year PFS also favored the group that started maintenance rituximab within 180 days post-ASCT (75% [95% CI, 60-85] vs 45% [95% CI, 35-54]; P <.001).

In the cohort of patients older than 65 years, maintenance rituximab was also associated with superior PFS and a trend toward improved OS. In patients whose disease status at ASCT was higher than first complete remission, maintenance rituximab was associated with both improved PFS and OS.

Forty-seven patients were transplanted with a disease status other than first complete remission. Five-year OS was 49% (95% CI, 33-63) in this group and 5-year PFS was 27% (95% CI, 15-41). For patients older than 65 at diagnosis (n = 40), 5-year OS and PFS were 68% (95% CI, 50-80) and 55% (95% CI, 38-69), respectively.

The 5-year cumulative incidence of relapse was 41% (95% CI, 34-48), with a continuous pattern of relapse events occurring at a median of 2.1 years after ASCT. A total of 83 relapses occurred at a median of 2.1 years posttransplant. Fourteen of 83 patients who relapsed subsequently underwent allogeneic transplant. Secondary malignancies occurred in 14 patients (7%), of which 5 were therapy-related myelodysplastic syndrome or acute myelogenous leukemia (3%). Nonrelapse mortality, defined as any death without a prior relapse, occurred in 16 patients (8%), and was a result of a secondary malignancy in 10 patients (5%).